Container

ABSTRACT

A container comprising a flexible semi-permeable composite membrane structure is described, as well as its applications. The membrane has a low molecular weight cut-off, comprises a flexible support layer thick enough to give strength to the membrane structure and having a relatively high molecular weight cut-off and, on at least one surface of the said support layer, a second layer having a relatively low molecular weight cut-off and is thin enough to allow a workable flux. Said container may be used for the preparation of rehydrated solute solutions, rehydrated blood or blood substitutes, nutritional solutions, solutions for medical purpose or of pure water.

FIELD OF THE INVENTION

The present invention is related to a new container useful for thepreparation of rehydrated solute solutions, of rehydrated bloodproducts, of nutritional solutions, of solutions for medical purpose orof pure water, comprising a semi-permeable membrane material with a lowmolecular weight cut-off, to its use in a process of osmotically drivenfiltration and for the manufacture thereof.

BACKGROUND OF THE INVENTION

In view of its intended uses, the wall of a container (or a portionthereof) useful for the preparation of rehydrated solute solutions, ofrehydrated blood products, of nutritional solutions, of solutions formedical purposes or of pure water by osmotically driven filtration,consists generally in a semi-permeable membrane.

Thus, a semi-permeable membrane needs to be strong, relatively inert andcapable of separating compounds with different molecular weights. Asemi-permeable membrane structure is characterized by its molecularweight cut-off (MWCO) defined by the molecular weight at which 90% ofthe solute will be prevented from permeating through the membrane. Sincethe permeability of a membrane with a given molecular weight cut-off isproportional to its thickness, the lower the molecular weight cut-off,the lower the thickness of the membrane must be to maintain practicalflux rates. However, the thinner this membrane becomes, the lower itsstrength. On the other hand, the higher the molecular weight cut-off,the more the phenomenon of dialysis can interfere with osmosis.Moreover, the lower the molecular weight cut-off, the more selective thesemi-permeable membrane. There are thus advantages of working with amolecular weight cut-off as low as possible while maximizing flux rate.

STATE OF THE ART

The European Patent EP 360612 discloses a process wherein an accuratelycontrolled mixture of low molecular sugar and electrolyte salts, whichtogether form the basis of an oral rehydration treatment, is retainedinto a leak proof container constructed from a semi-permeable membranewhich may be of cellulose, regenerated cellulose, benzoylated cellulose,viscose cellulose and collagen. This membrane has a molecular weightcut-off below the molecular size of microorganisms or enterotoxins of V.Cholerae and Shigella species so that when the container and contentsare placed into water containing the said contaminants, a process ofosmosis takes place where water free from contaminants is drawn into thecontainer, but where the passage of micro-organism into the container isprevented, resulting in a sterile oral rehydration solution inside thecontainer. In this disclosure, the concentration of the sterile contentof the container is controlled by achieving an equilibrium between theosmosis and dialysis of the sugars and electrolytes into the externalwater. Therefore, the final concentration of solution is dictated by thequantity of solute within the container and the volume of externalwater. The disadvantages of this system are an expensive loss of solute,the growth of bacteria in the external water due to sugars (nutrient)feeding, the need to precisely control the volume of external water andthe low efficiency of the device, i.e. amount of water taken up in agiven period being low due to dialysis of solute.

Aims of the Invention

The present invention aims to provide a container which does not presentthese drawbacks. The aim of the invention is to provide a containercomprising a flexible membrane structure, wherein the membrane has a lowmolecular weight cut-off (allowing to eliminate or minimize the dialysisof solutes) and has an increased selectivity.

As lowering the molecular weight cut-off of the membrane results in asevere decrease in speed of operation of the device, reducing thethickness of the membrane to compensate for the reduction in speedresults in an impracticably weak structure. It is therefore an aim ofthe present invention to provide a container comprising as membrane, athick and strong film with a relatively high average pore diameter andnumber as a support for a thin layer with a relatively low molecularweight cut-off. This enables one to tune the selectivity of thecomposite membrane structure whilst maximizing flux.

It is a further aim of the present invention to substantially reducedialysis which enables solutions of concentrations within the requiredtolerance to be obtained in a shorter period of time without the needfor the precise measurement of the outer volume of water, by means of acontainer comprising a membrane having a first layer with very largepores which can be utilized as a support for a thin polymeric layercoated onto the surface of the first layer. The resultant reduction ofdialysis also leads to considerably lower increase in external waterbacteria count.

A further aim of the invention is to provide a device allowing thepreparation of rehydrated solute solutions, of rehydrated bloodproducts, of nutritional solutions, of solutions for medical purpose orof pure water into a closed container, especially in conjunction withthe process of osmotically driven ultrafiltration as described in theEuropean Patent No. 360612. It is however to be noted that the containeraccording to the invention may be efficiently placed into flowing water(stream, river and the like) or into stagnant water (lake, pool and thelike).

Description of the Invention

The invention is related to a container for the preparation ofrehydrated solute solutions, rehydrated blood or blood substitutes,nutritional solutions, solutions for medical purpose or of pure watercomprising a flexible semi-permeable composite membrane structure havinga low molecular weight cut-off and at least one water soluble solidcontained therein, which membrane comprises a flexible support layerthick enough to give strength to the membrane structure and having arelatively high molecular weight cut-off and on at least one face of thesaid support layer, a second layer having a relatively low molecularweight cut-off and being thin enough to allow a workable flux.

By container, it is to be understood a closed structure; for example inthe form of a bag or a pouch.

By flexible membrane is understood a structure which is capable offurther shaping and which is also flexible, either prior or after beingbrought in contact with water.

By thick enough to give strength to the membrane structure, it is to beunderstood that the membrane should be strong enough to prevent damageswhen both dry or swollen with water. By thin enough to allow a workableflux, it is to be understood that the flux should be at least 0.1l/h.m2.bar.

The molecular-weight cut-off of the two layers to be chosen may varywithin a large range.

The MWCO of the support layer is chosen in order to allow a high fluxand yet to prevent the passage through the membrane of microorganismsfrom the outside water. One may thus select for the support layer, afilm which has relatively large pores, for examples of between 2 and 20nm of diameters. On the other hand, the MWCO of the second layer ischosen in order to prevent dialysis of low molecular weight solutes. Thepore size of the support layer can thus be many times that of the secondlayer. Preferably, the molecular weight cut-off of the support layer isfrom 1,000 to 50,000 and/or the molecular weight cut-off of second layeris from 300 to 2,000.

As a matter of fact, it is to be noted that the entering flux of wateris lowered by the thin second layer. The flux for a simple regeneratedcellulose film is from 1.7 to 3 l/h.m2.bar and may be as low as 0.1l/h.m2.bar for the composite film of the invention. However,surprisingly, for the composite films of the invention, as the dialysis(thus the coming out flux) is even more decreased, the resulting flux ispositive and considerably increased. The relative thickness of thecomponents of the composite membrane structure will be determined by therequired flux rate and strength.

Preferably, the overall thickness of the composite membrane is from 20to 50 μm; the thickness of the support layer is from 19 to 48 μm and thethickness of the second layer is from 0.1 to 2.0 μm.

The support layer can be selected from a wide variety of materialsincluding cellulose, regenerated cellulose (CELLOPHANE®, cuprammoniumcellulose), benzoylated cellulose and collagen.

The preferred material for the support layer is regenerated cellulose.The support layer may be produced by one or several known manufacturingmethods, such as xanthate, cuprammonium, carbamate or organic solvent(e.g. NMMO) processes when a regenerated cellulose material is used.

The second layer can be composed of cellulose derivatives (e.g. ethers,esters, nitrocellulose, etc.), synthetic organic polymers (e.g.polyacrylic ester, polyvinyl acetate copolymers, polyurethanes,aliphatic polyamides such as nylon 6, nylon 6.6, nylon 4.6, polysulfoneand polyethersulfone and the like), modified or unmodified naturallyoccurring polymers (e.g. starches, proteins, etc.). Mixture of thesewith or without the addition of inorganic additives (e.g. fumed silica)can also be used.

However, the most interesting results have been obtained withpolyurethanes conventionally used for covering textile with a protectivewaterproof but water vapor permeable coating. It is particularlysurprising that a waterproof membrane may be used to filter aqueousmedium.

Hydrophilic polyurethanes which may be used according to the inventionas preferred material for the second membrane are the reaction productof

(a) polyisocyanates; and

(b) polyols containing at least two isocyanate reactive groups; and

(c) optionally an active hydrogen-containing chain extender.

Suitable polyisocyanates comprise aliphatic, cycloaliphatic, or aromaticpolyisocyanates. As examples of suitable aliphatic diisocyanates, theremay be mentioned 1,4-diisocyanatobutane, 1,6-diisocyanatohexane,1,6-diisocyanato-2,2,4-trimethylhexane and 1,12-diisocyanatododecaneeither alone or in admixture. Particularly suitable cycloaliphaticdiisocyanates include 1,3- and 1,4-diisocyanatocyclohexane,2,4-diisocyanato-1-methylcyclohexane,1,3-diisocyanato-2-methylcyclohexane,1-isocyanato-2-(isocyanatomethyl)cyclopentane,1,1′-methylenebis[4-isocyanatocyclohexane],1,1′-(1-methylethylidene)bis[4-isocyanatocyclohexane],5-isocyanato-1-isocyanatomethyl-1,3,3-trimethylcyclohexane (isophoronediisocyanate), 1,3- and 1,4-bis(isocyanatomethyl)cyclohexane,1,1′-methylenebis[4-isocyanato-3-methylcyclohexane], 1-isocyanato-4(or3)-isocyanatomethyl-1-methylcyclohexane either alone or in admixture.Particularly suitable aromatic diisocyanates include1,4-diisocyanatobenzene, 1,1′-methylenebis[4-isocyanatobenzene],2,4-diisocyanato-1-methylbenzene, 1,3-diisocyanato-2-methylbenzene,1,5-diisocyanatonaphthalene,1,1′-(1-methylethylidene)bis[4-isocyanatobenzene], 1,3- and1,4-bis(1-isocyanato-1-methylethyl)benzene, either alone or inadmixture. Aromatic polyisocyanates containing 3 or more isocyanategroups may also be used such as 1,1′,1″-methylidynetris[4-isocyanatobenzene] and polyphenyl polymethylenepolyisocyanates obtained by phosgenation of aniline/formaldehydecondensates. The polyols containing at least two isocyanate reactivegroups may be polyester polyols, polyether polyols, polycarbonatepolyols, polyacetal polyols, polyesteramide polyols or polythioetherpolyols. The polyester polyols, polyether polyols and polycarbonatepolyols are preferred.

Suitable polyester polyols which may be used include thehydroxyl-terminated reaction products of polyhydric, preferably dihydricalcohols (to which trihydric alcohols may be added) with polycarboxylic,preferably dicarboxylic acids or their corresponding carboxylic acidanhydrides. Polyester polyols obtained by the ring openingpolymerization of lactones such as e-caprolactone may also be included.

The polycarboxylic acids which may be used for the formation of thesepolyester polyols may be aliphatic, cycloaliphatic, aromatic and/orheterocyclic and they may be substituted (e.g. by halogen atoms) andsaturated or unsaturated. As examples of aliphatic dicarboxylic acids,there may be mentioned, succinic acid, glutaric acid, adipic acid,suberic acid, azelaic acid, sebacic acid and dodecanedicarboxylic acid.As an example of a cycloaliphatic dicarboxylic acid, there may bementioned hexahydrophthalic acid. Examples of aromatic dicarboxylicacids include isophthalic acid, terephthalic acid, ortho-phthalic acid,tetrachlorophthalic acids and 1,5-naphthalenedicarboxylic acid. Amongthe unsaturated aliphatic dicarboxylic acids which may be used, theremay be mentioned fumaric acid, maleic acid, itaconic acid, citraconicacid, mesaconic acid and tetrahydrophthalic acid. Examples of tri- andtetracarboxylic acids include trimellitic acid, trimesic acid andpyromellitic acid.

The polyhydric alcohols which may be used for the preparation of thepolyester polyols include ethylene glycol, propylene glycol,1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol,1,6-hexanediol, neopentyl glycol, diethylene glycol, dipropylene glycol,triethylene glycol, tetraethylene glycol, dibutylene glycol,2-methyl-1,3-pentanediol, 2,2,4-trimethyl- 1,3-pentanediol,1,4-cyclohexanedimethanol, ethylene oxide adducts or propylene oxideadducts of bisphenol A or hydrogenated bisphenol A. Triols or tetraolssuch as trimethylolethane, trimethylolpropane, glycerine andpentaerythritol may also be used. These polyhydric alcohols aregenerally used to prepare the polyester polyols by polycondensation withthe above-mentioned polycarboxylic acids, but according to a particularembodiment they can also be added as such to the reaction mixture.

Suitable polyether polyols include polyethylene glycols, polypropyleneglycols and polytetraethylene glycols.

Suitable polycarbonate polyols which may be used include the reactionproducts of diols such as 1,3-propanediol, 1,4-butanediol,1,6-hexanediol, diethylene glycol, triethylene glycol or tetraethyleneglycol with phosgene, with diarylcarbonates such as diphenylcarbonate orwith cyclic carbonates such as ethylene and/or propylene carbonate.

Suitable polyacetal polyols which may be used include those prepared byreacting glycols such as diethyleneglycol with formaldehyde. Suitablepolyacetals may also be prepared by polymerizing cyclic acetals.

The active hydrogen-containing chain extender which may optionally beused is suitably an aliphatic, alicyclic, aromatic or heterocyclicprimary or secondary polyamine having up to 80, preferably up to 12carbon atoms, or water. In the latter case, a fully reacted polyurethanepolymer is obtained with no residual free isocyanate groups.

Where the chain extension of the polyurethane prepolymer is effectedwith a polyamine, the total amount of polyamine should be calculatedaccording to the amount of isocyanate groups present in the polyurethaneprepolymer in order to obtain a full, reacted polyurethaneurea polymerwith no residual free isocyanate groups; the polyamine used in this casehas an average functionality of 2 to 4, preferably 2 to 3.

The degree of non-linearity of the polyurethaneurea polymer iscontrolled by the functionality of the polyamine used for the chainextension. The desired functionality can be achieved by mixingpolyamines with different amine functionalities. For example, afunctionality of 2.5 may be achieved by using equimolar mixtures ofdiamines and triamines.

Examples of such chain extenders useful herein include hydrazine,ethylene diamine, piperazine, diethylene triamine, triethylenetetramine, tetraethylene pentamine, pentaethylene hexamine,N,N,N-tris(2-aminoethyl)amine, N-(2-piperazinoethyl)ethylenediamine,N,N′-bis(2-aminoethyl)piperazine,N,N,N′-tris(2-aminoethyl)ethylenediamine,N-[N-(2-aminoethyl)-2-aminoethyl]-N′-(2-aminoethyl)piperazine,N-(2-aminoethyl)-N′-(2-piperazinoethyl)ethylenediamine,N,N-bis(2-aminoethyl)-N-(2-piperazinoethyl)amine,N,N-bis(2-piperazinoethyl)amine, guanidine, melamine,N-(2-aminoethyl)-1,3-propanediamine, 3,3′-diaminobenzidine,2,4,6-triaminopyrimidine, dipropylenetriamine, tetrapropylenepentamine,tripropylenetetramine, N,N-bis(6-aminohexyl)amine,N,N′-bis(3-aminopropyl)ethylenediamine, 2,4-bis(4′-aminobenzyl)aniline,1,4-butanediamine, 1,6-hexanediamine, 1,8-octanediamine,1,10-decanediamine, 2-methylpentamethylenediamine, 1,12-dodecanediamine,isophorone diamine (or1-amino-3-aminomethyl-3,5,5-trimethyl-cyclohexane),bis(4-aminocyclohexyl)methane [or bis(aminocyclohexane-4-yl)-methane]and bis(4-amino-3-methylcyclohexyl)methane [orbis(amino-2-methylcyclohexane-4-yl)methane], polyethylene imines,polyoxyethylene amines and/or polyoxypropylene amines (e.g. Jeffaminesfrom TEXACO).

The total amount of polyamines should be calculated according to theamount of isocyanate groups present in the polyurethane prepolymer. Theratio of isocyanate groups in the prepolymer to active hydrogens in thechain extender during the chain extension is in the range of from about1.0:0.7 to about 1.0:1.1, preferably from about 1.0:0.9 to about1.0:1.02 on an equivalent basis.

Preferably, the polyisocyanate is a diisocyanate and more preferably itis selected from 1,1′-methylenebis-[4-isocyanatobenzene]and1,1′-methylenebis-[4-isocyanatocyclohexane].

Preferably the polyol is a polyethyleneglycol selected fromethyleneglycol, polyethyleneglycol, polytetramethyleneglycol and thelike, eventually in admixture with other polyether polyols.

Even more preferably, the polyethylene glycol has a very low molecularweight (from 300 to 900). This is rather unconventional as usually thepolyurethanes incorporate polyethylene glycol with a molecular weightabove 2000 in order to achieve the well known properties of thepolyurethanes (long soft and hard segments, melting point, strength).Breathability is also known to decrease with the molecular weight of thepolyethylene glycol. However, in this embodiment, the low molecularweight of the polyethylene glycol is supposed to be responsible for theamelioration of the flux.

Preferably the chain extender is isophorone diamine (or1-amino-3-aminomethyl-3,5,5,-trimethylcyclohexane) alone or in admixturewith hydrazine.

The second layer can be applied to the support layer by coating from asolution, lamination, extrusion coating or in-situ polymerization ontoeither or both surfaces of the support membrane.

The composite membrane according to the invention is mainly intended anddevised for osmotically driven ultrafiltration, but other uses of themembrane according to the invention includes reverse osmosisapplication, vacuum or pressure filtration, biological separation (e.g.virus separation from body fluids), gas separation, effluent treatment,water filtration, control drug release system, etc.

The membranes of the invention are particularly suited for osmoticallydriven ultrafiltration as they permit to lower the MWCO to a level lowenough to prevent dialysis to interfere with osmosis, while the fluxremains acceptable. A broader range of solute with a lower MWCO can thusbe prevented from leaving through the filtration membrane. A typicalapplication of this particular process is a self rehydrating closedosmotic bag. This bag consists of a container comprising as externalwall the composite semi-permeable membrane structure according to theinvention and a solute to be rehydrated retained into said container. Inanother embodiment of the invention. the new membrane is just a portionof the external wall. Suitable container properties are disclosed indetail in EP 360612.

The container retains the solute either as a solid or a concentratedsolution. When the closed bag is contacted with water, water diffusesthroughout the membrane and brings the solute in solution (very limitedphenomenon). Once a highly concentrated solution is obtained in the bag,osmosis takes over and literally pumps external water into the bag. Itis therefore a prerequisite that at least one water soluble solute ispresent in the bag for osmosis to occur.

Either the solute comprises water soluble compounds with a molecularweight higher than the low MWCO of the second membrane, thus allowing toprepare solute solutions such as rehydrated nutritional substances likemilk powder or fruit juice, rehydrated blood products, medicaments ororal rehydration compositions or the solute only comprises water solublecompounds with a molecular weight lower than the low MWCO of the secondmembrane, thus allowing to prepare substantially pure water, which canbe used for medical purposes for example.

In a particularly advantageous variant, the solute may comprise amixture of water soluble compounds with molecular weights higher andlower than the MWCO of the second layer. In this case, the compoundswith a molecular weight lower than the MWCO of the second layercontribute mainly to initiate promptly the osmosis phenomenon, while thefinal solution consists essentially of the compounds having a molecularweight higher than the MWCO of the second layer.

The following examples are given for the purpose of illustrating thepresent invention.

EXAMPLES

1. Material for the second layer.

1.1 Commercial materials

1.1.1 Nitrocellulose grade A 500 (BAYER AG)

1.1.2 Nitrocelllulose DML 30/50 (ICI)

1.2 Specifically devised material

1.2.1 A solution of 85.50 g of a polyethyleneglycol (PEG 2000 (INSPEC))having a molecular weight of about 2000, 72.80 g of apoly(tetramethyleneglycol) (TERATHANE 2000 (DUPONT)) having a molecularweight of about 2000, 21.24 g of ethyleneglycol and 105.46 g of1,1′-methylenebis(4-isocyanatobenzene) in a mixture of 420 g ofdimethylformamide and 65 g of methylethylketone is introduced into a2-liter four necked round bottomed flask equipped with a mechanicalstirrer, a thermometer, an air condenser, a nitrogen inlet and adropping funnel. The mixture is heated at 90° C. while stirring and 0.15g of tin 2-ethylhexanoate (DABCO T9 (AIR PRODUCTS)) as catalyst, isintroduced. The reaction mixture is maintained at 90° C. for 2 hours andthen cooled.

120 g of methylethylketone are then introduced into the reaction vessel.

1.2.2 A solution of 133.02 g of polyethyleneglycol (PEG 600 (HOECHST))having a molecular weight of about 600 and 79.00 g of1,1′-methylenebis(4-isocyanatocyclohexane) in 342.00 g of toluene isintroduced into a 2-liter four necked round bottomed flask equipped witha mechanical stirrer, a thermometer, an air condenser, a nitrogen inletand a dropping funnel.

The mixture is heated at 90° C. while stirring and 25 mg ofdibutyltinlaurate (DABCO T12 (AIR PRODUCTS)), as catalyst, isintroduced. The reaction mixture is maintained at 90° C. for 6 hours andthen cooled.

A solution of 13.68 g of isophrone diamine in 350.00 g of isopropylalcohol is introduced in a second 2-liter four necked round bottomedflask equipped with a mechanical stirrer, a thermometer, an aircondenser, a nitrogen inlet and a droppind funnel.

The content of the first flask is cooled at room temperature and is thenadded slowly to the mixture alcohol/amine (second flask). Chainextension is complete after about 3 hours. 44.2 g or fumed silica (TS100DEGUSA) and 50 g of toluene are added to the mixture.

1.2.3 A solution of 114.40 g of polyethyleneglycol having a molecularweight of about 400 (PEG 400 (HOESCHT)), 20.60 g ofpoly(tetramethyleneglycol) having a molecular weight of about 1000(TERATHANE 1000 (DUPONT)) and 106.80 g of1,1′-methylenebis(4-isocyanatocyclohexane) in 342.00 g of toluene isintroduced into a 2-liter four necked round bottomed flask equipped witha mechanical stirrer, a thermometer, an air condenser, a nitrogen inletand a dropping funnel.

The rest of the process is as in example 1.2.2 but the isopropyl alcoholis replaced with ethyl alcohol, the isophorone diamine is replaced witha mixture of 11.35 g of isophorone diamine and 7.12 g of an aqueoussolution of hydrazine (15% (w)) and the toluene is replaced withethylacetate.

2. Preparation of the membrane.

Membranes have been prepared by coating regenerated cellulose films(thickness of around 35 μm) with different molecular weight cut-off withthe different materials cited at point 1. The coating (about 1 μm (dry))are applied by direct gravure coating at 10 g/m2 (wet weight). Thefollowing membranes have been prepared

TABLE I Material of example: No coating 1.1.1 1.2.1 1.2.2 1.2.3 RCF MWCO1800 2.1 (1) 2.3 2.4 2.7 2.10 (viscose 9.5%) RCF MWCO 2500 2.5 2.8 2.11(viscose 7.5%) RCF Mwco 2500 2.2(1) 2.6 2.9 2.12 (viscose 6%) RCF:regenerated cellulose film (1): by way of comparison

3. Preparation of osmotic bag

Bags have been prepared from the membranes made out at example 2.

The following solute compositions have been prepared:

A. Sucrose 38 g

Sodium citrate dihydrate 2.9 g

A2 Sucrose 76 g

Sodium citrate dihydrate 5.8 g

B. Sucrose 35 g

Sodium citrate dihydrate 2.9 g

C. Sucrose 27 g

Sodium citrate dihydrate 1.7 g

D. Sucrose 29 g

Sodium citrate dihydrate 2.9 g

Rectangular closed bags having dimension of 210×110 mm containing thecompositions A, A2, B or C have been prepared:

3.1 membrane prepared at example 2.1 filled with composition A (1);

3.2 membrane prepared at example 2.1 filled with composition A2(1);

3.3 membrane prepared at example 2.2 filled with composition A (1);

3.4 membrane prepared at example 2.2 filled with composition A2(1);

3.5 membrane prepared at example 2.7 (coating on the inner side of thebag) filled with composition B;

3.6 membrane prepared at example 2.9 (coating on the inner side of thebag) filled with composition D;

3.7 membrane prepared at example 2.11 (coating on the inner side of thebag) filled with composition C;

3.8 membrane prepared at example 2.12 (coating on the inner side of thebag) filled with composition C;

(1) by way of comparison

4. Preparation of purified solutions

The bags prepared at example 3 are immersed in water which contains E.Coli (NCI.B86 wild type around 5.6×106 cfu/ml).

The following table shows the results

TABLE II time to reach the final concentration in final conc.equilibrium in losses in bacteria the required by sodium in external Baglevel volume sucrose dialysis citrate water 3.1 24 h 267.8 ml 44.7 g/l68% 3.16 g/l 1.108 cfu/ml 3.2 24 h 503.0 ml 58.8 g/l 61% 3.66 g/l — 3.324 h 295.6 ml 41.6 g/l 67% 3.0 g/l — 3.4 24 h 574 ml 46.8 g/I 65% 3.18g/l — 3.5 17.5 h 499.4 ml 32.2 g/l 54% 3.2 g/l — 3.6 8 h 518 ml 42 g/l19% 2.92 g/l — 3.7 9 h 500 ml 42 g/l 23% 3.0 g/l — 3.8 9.5 h 496.4 mI 42g/l 23% 3.0 g/l —

It appears from Table II that in the absence of the second membrane, theincrease in MWCO results in a better flux (after an equivalent period oftime, the bag with the largest MWCO contains 10% more water). In bothcases, the lost of solute are ven, important (about 70%).

It is also noted that with a second membrane, the flux is more thandoubled, which results in a greater volume collected in the bag in ashorter period of time. It is also noted that in this case the lost ofsolute is considerably lowered.

Finally it appears clearly from the comparison between the bags 3.5 and3.8 that the best results are obtained when the membrane has been madewith a first support layer with large pores which has been coated with asecond layer of hydrophilic polyurethane.

What is claimed is:
 1. Container for the preparation of rehydratedsolute solutions, rehydrated blood or blood substitutes, nutritionalsolutions, solutions for medical purpose or of pure water comprising aflexible semi-permeable membrane and at least one water soluble solidretained therein, wherein the flexible semi-permeable membrane is acomposite membrane structure having a low molecular weight cut-off,comprising a flexible support layer thick enough to give strength to themembrane structure and having a molecular weight cut-off from 1,000 to50,000, and on at least one surface of the said support layer, a secondlayer having a molecular weight cut-off from 300 to 2,000 and being thinenough to allow a flux of at least 0.1 l/hr.m².bar.
 2. Containeraccording to claim 1 wherein the wall of said container consistsessentially of said flexible semi-permeable membrane.
 3. Containeraccording to claim 1 wherein only a portion of the wall consists of saidflexible semi-permeable membrane.
 4. Container according to claim 1wherein the support layer of the membrane is a semi-permeable materialselected from the group consisting of cellulose, regenerated cellulose,benzoylated cellulose and collagen.
 5. Container according to claim 1wherein the second layer of the membrane is a film of a materialselected from the group consisting of cellulose derivative, syntheticorganic polymer, naturally occurring polymer, modified naturallyoccurring polymer, and a mixture thereof.
 6. Container according toclaim 5 wherein the second layer of the membrane is a hydrophilicpolyurethane film.
 7. Container according to claim 1 wherein the secondlayer of the membrane is applied on at least one surface of said supportlayer by a process selected from solution coating, lamination, extrusioncoating and in-situ polymerization.
 8. Container according to claim 1wherein the second layer of the membrane is applied on both surfaces ofsaid support layer.
 9. Process for the preparation of rehydrated solutesolution of rehydrated blood or blood substitutes, of nutritionalsolutions, of solutions for medical purpose, or of pure water, wherein acontainer according to claim 1 is placed in water.
 10. Process for thepreparation of a rehydrated solute solution, of rehydrated blood orblood substitute, of a nutritional solution, of a solution for medicalpurpose or of pure water with a container according to claim 1 whereinsaid container is placed for a sufficient period of time in flowing orstagnant water.